Porcine familial adenomatous polyposis model enables systematic analysis of early events in adenoma progression

Abstract

We compared gene expression in low and high-grade intraepithelial dysplastic polyps from pigs carrying an APC 1311 truncating mutation orthologous to human APC 1309, analysing whole samples and microdissected dysplastic epithelium. Gene set enrichment analysis revealed differential expression of gene sets similar to human normal mucosa versus T1 stage polyps. Transcriptome analysis of whole samples revealed many differentially-expressed genes reflecting immune infiltration. Analysis of microdissected dysplastic epithelium was markedly different and showed increased expression in high-grade intraepithelial neoplasia of several genes known to be involved in human CRC; and revealed possible new roles for GBP6 and PLXND1. The pig model thus facilitates analysis of CRC pathogenesis.